Fusion protein technology, i.e., expressing in a host cell a target protein fused with a protein partner, allows for enhanced expression of the target protein, which is protected from degradation/mis-folding, easy to be purified/detected, and has improved solubility. The protein partner usually would interfere with the structural or functional properties of the target protein and therefore needs to be removed via, e.g., chemical or enzymatical cleavage, from a fusion protein to generate a free target protein. Cleavage of the protein partner remains the major disadvantage in conventional fusion technology as imprecise cleavage, which occurs frequently, results in failure to recover an active or structurally intact target protein.
The newly developed small-ubiquitin-related modifier (SUMO) fusion technology makes up for this disadvantage. In a SUMO fusion expression system, the fusion partner, i.e., a SUMO protein, can be precisely removed by a SUMO protease, thereby generating a native target protein. See, e.g., Butt et al., Protein Expression and Purification 43:1-9 (2005) and Mossessova et al., Molecular Cell 5:865-876 (2000).